Modulation of gap junction coupling in the vertebrate retina

脊椎动物的视网膜是排列在眼睛后部的一层薄薄的中枢神经系统组织，它将视觉世界的图像转换为电化学信号，并对该信号进行处理，产生编码视觉场景不同方面的平行路径。缝隙连接是细胞间直接电耦合的结构关联，是脊椎动物视网膜回路的重要参与者。下面的研究集中在脊椎动物视网膜缝隙连接耦合的两个不同方面。首先，我们建议通过关注神经调节剂多巴胺的潜在新来源来继续我们对硬骨视网膜中视网膜水平细胞耦合的调制的研究。其次，我们将进一步研究哺乳动物视网膜中一种新型的神经节细胞--固有的对光敏感的含有黑素的神经节细胞--的偶联。 多巴胺(DA)是最著名的水平细胞活动的神经调节剂。直到最近，硬骨视网膜内源性多巴胺的唯一已知来源是网状细胞。最近发现了视网膜中DA的一个可能的额外来源。这一来源是视网膜色素上皮(RPE)，在那里，DA前体L-多巴可以被酪氨酸酶合成，这是与RPE黑色素合成相关的合成途径的一部分。我们打算通过检测硬骨视网膜的两个已知的依赖DA和光的特征，视锥细胞的移动和水平细胞的耦合来研究DA的潜在来源。这些研究将使用缺乏酪氨酸酶的斑马鱼突变体和使用酪氨酸酶抑制剂处理的金鱼，并将使用解剖学和电生理学技术。 以往的研究表明，内源性光敏视网膜神经节细胞(IpRGCs)是缝隙连接耦合的。我们已经发表了解剖学证据，证明ipRGC与视网膜中一类特定的无长突细胞相连。我们打算利用钙成像来确定这种偶联是否可以在生理上得到证实，并试图确定ipRGC表达的缝隙连接的类型。

The vertebrate retina is a thin sheet of central nervous system tissue lining the back of the eye that transduces the image of the visual world into an electrochemical signal and processes this signal generating parallel pathways encoding different aspect of the visual scene. Gap junctions, the structural correlate of direct electrical coupling between cells, are important participants in the circuitry of the vertebrate retina. The following research focuses on two different aspects of gap junction coupling in the vertebrate retina. First, we propose to continue our studies of the modulation of retinal horizontal cell coupling in the teleost retina by focusing on a potential new source of the neuromodulator dopamine. Second, we will further our study of the coupling of a new type of ganglion cell, the intrinsically light-sensitive, melanopsin-containing ganglion cells, in the mammalian retina. Dopamine (DA) is the best-known neuromodulator of horizontal cell activity. Until recently, the only known source of endogenous dopamine in the teleost retina was interplexiform cells. A possible additional source of DA in the retina has recently been identified. This source is the retinal pigmented epithelium (RPE), where the DA precursor L-DOPA could be synthesized by tyrosinase as part of the synthetic pathway associated with the synthesis of the RPE pigment melanin. We intend to study this potential source of DA by examining two known DA- and light-dependent features of the teleost retina, the movement of cones and the coupling of horizontal cells. These studies will use a zebrafish mutant that lacks tyrosinase and goldfish treated with tyrosinase inhibitors and will employ both anatomical and electrophysiological techniques. Previous work suggests that the intrinsic photosensitive retinal ganglion cells (ipRGCs) are gap junction coupled. We have published anatomical evidence that ipRGCs are coupled to a specific class of amacrine cells in the retina. We intend to determine if this coupling can be demonstrated physiologically, using calcium imaging, and will attempt to identify the type of gap junction that ipRGCs express.